ABLi Therapeutics Partners with Michael J. Fox Foundation to Test Risvodetinib in Parkinson's Prevention Trial
核心洞察
ABLi Therapeutics (搜索) has entered a collaboration agreement with The Michael J. Fox Foundation (搜索) to include risvodetinib in the Path to Prevention (P2P) platform trial for prodromal Parkinson's disease (搜索).
The P2P trial is a Phase 2, randomized, double-blind, placebo-controlled study that will investigate multiple investigational therapies in participants with biomarker characteristics of Parkinson's disease (搜索) who have not yet progressed to a full diagnosis.
Risvodetinib is a selective c-Abl kinase inhibitor that previously demonstrated disease-modifying potential in a Phase 2 trial and is believed to be the first therapy to improve patient quality of life while simultaneously reducing alpha-synuclein (搜索) pathology.
ABLi Therapeutics (搜索) has entered into a collaboration agreement with The Michael J. Fox Foundation (搜索) for Parkinson's Research (MJFF) to include its lead candidate risvodetinib in the Foundation's Path to Prevention (P2P) platform trial. The multi-arm P2P trial, expected to launch in the coming months, will investigate the safety and efficacy of several investigational agents in participants who have biomarker characteristics of Parkinson's disease (搜索) but have not yet progressed to a full diagnosis.
Novel Prevention-Focused Trial Design
The P2P platform trial will be built on top of the Parkinson's Progression Marker Initiative (PPMI) study, which was launched in 2010 to identify biomarkers and better understand Parkinson's disease (搜索) progression. P2P is designed as a platform, randomized, double-blind, placebo-controlled, multi-center Phase 2 trial planned to study disease progression in hundreds of patients over a period of two to three years using multiple investigational therapies from companies developing potential disease-modifying therapeutics.
The trial will focus on a unique patient population: prodromal participants with early clinical signs of Parkinson's disease (搜索) who have both pathological alpha-synuclein (搜索) measured by the Seed Amplification Assay (SAA) and dysfunction of dopamine neurotransmission by DAT-SPECT imaging, but who do not have a clinical diagnosis of Parkinson's disease or related disorders. The ultimate goal of P2P is to measure whether tested therapies show efficacy in preventing progression to a formal diagnosis of Parkinson's disease.
Risvodetinib's Unique Mechanism and Previous Results
Risvodetinib (ABLi-148009) is a potent, selective small-molecule inhibitor of the non-receptor c-Abl kinases (搜索), designed for once-daily oral use that targets the underlying biological mechanisms driving Parkinson's disease (搜索) initiation and progression. The drug is believed to be a disease-modifying therapy that halts disease progression and reverses the functional loss arising from Parkinson's disease inside and outside of the brain.
According to ABLi, risvodetinib is the first therapy that does not involve dopamine replacement to improve patient quality of life in a randomized, placebo-controlled clinical trial (NCT05424276) and simultaneously reduced the underlying alpha-synuclein (搜索) aggregate pathology in untreated Parkinson's disease (搜索). The company completed a Phase 2 201 Trial that assessed the safety, tolerability and disease-modifying potential of risvodetinib in participants with early untreated Parkinson's disease.
Parallel Development Strategy
"Following the successful completion of the Phase 2 201 Trial that assessed the safety, tolerability and disease-modifying potential of risvodetinib in participants with early untreated PD, we are excited to be the first of several companies to enter into a collaboration agreement to join the Foundation's P2P trial," said Dr. Milton Werner, Chairman and Chief Executive Officer of ABLi. "We believe risvodetinib may be disease-modifying based on synuclein biomarker data. We're excited to have the opportunity to evaluate the effect of risvodetinib even earlier in the disease course through P2P."
The P2P trial will run alongside ABLi's registration trial for risvodetinib, known as the C-Abl inhibitor Modification of Parkinson's Disease (搜索) trial (CAMPD), in early untreated Parkinson's disease. Christopher Meyer, Chief Operating Officer and Head of Development Operations of ABLi, explained that "the primary endpoint for CAMPD is intended to directly measure the ability of risvodetinib to delay disease progression in hundreds of patients within three years of a Parkinson's diagnosis."
Addressing Unmet Medical Need
The collaboration addresses a significant unmet medical need in Parkinson's disease (搜索) treatment. According to ABLi, all marketed therapeutic approaches to treat Parkinson's help manage the symptoms of the disease, but there are currently no available treatments to slow or stop the disease's relentless progression.
The P2P study has multiple primary endpoints, including clinical and biomarker endpoints. Novel biomarkers specific to risvodetinib and developed by ABLi and its collaborators are being evaluated for inclusion in the risvodetinib study arm. Risvodetinib currently has intellectual property protection beyond 2036.
ABLi Therapeutics (搜索) focuses on developing small molecule therapeutics that target diseases arising from activation or dysfunction of the Abelson Tyrosine Kinases (c-Abl). The company's primary focus is on developing therapeutics for neurodegenerative diseases like Parkinson's disease (搜索) and related conditions including Multiple System Atrophy (搜索) and Dementia with Lewy Body (搜索), which are all associated with Abl kinase activation or dysfunction.